| 15621283 |
Colangelo D, Ghiglia A, Ghezzi A, Ravera M, Rosenberg E, Spada F, Osella D: Water-soluble benzoheterocycle triosmium clusters as potential inhibitors of telomerase enzyme. J Inorg Biochem. 2005 Feb;99(2):505-12.
We have studied the ability of several bioorganometallic clusters [(mu-H) Os (3)(CO)(9)(L)(mu (3)-eta (2)-(Q-H))], where L = [P (C (6) H (4) SO (3) Na)(3)] or [P (OCH (2) CH (2) NMe (3) I)(3)], and Q = quinoline, 3-aminoquinoline, quinoxaline or phenanthridine, of inhibiting telomerase, a crucial enzyme for cancer progression. In general, quinolines have shown interesting biological properties, especially in inhibiting enzymes. For example, the 2,3,7-trichloro-5-nitroquinoxaline (TNQX) exhibited strong anti-telomerase activity in vitro. Among the quinoline-clusters under study, only the negatively charged ones (by virtue of the sulfonated phosphines) exhibited good anti-telomerasic activity on semi-purified enzyme in a cell-free assay, while they were ineffective in vitro on Taq, a different DNA-polymerase. On the contrary, the treatment of breast cancer MCF-7 cell line did not evidence any activity of these clusters, suggesting a low aptitude for crossing cell membrane. Furthermore, all clusters exhibited non-specific, acute cytotoxicy, probably due to accumulation on cell membranes by virtue of their amphiphilic character. A detailed study of Os uptake and accumulation in MCF-7 cells supported this hypothesis. |
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